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Hello and welcome to the October
episode of Chattering with ISFM.

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I'm Nathalie Dowgray, Head of ISFM
and host of this month's podcast.

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This month, Kelly St Denis is going
to be speaking with Jonathan Stockman

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about his JFMS Clinical Spotlight
article, Where Are We With Dietary

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Phosphorus and Renal Disease?

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But first up this month, Yaiza Gomez
Mejias is speaking with Sina Marsilio

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on the latest in feline chronic
enteropathies, including GI lymphoma.

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Which are the different types
of cells involved in feline

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gastrointestinal lymphoma?

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This lymphoma is made of
small, mature lymphocytes.

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That's important to realise in
contrast to the classic multi centric

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lymphoma that we see in dogs where
they show up with big lymph nodes.

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That's not the case for low grade
intestinal T cell lymphoma or LGITL, the

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cells are mature small T lymphocytes.

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This lymphoma makes up about
75 to 80 percent of all

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feline intestinal lymphomas.

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These lymphocytes are about the size
of a neutrophil, these cells mostly

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affect the mucosa, either the lamina
propria or the epithelium, in which

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case we talk about an epitheliotropic
lymphoma, or they can be also mixed.

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In the duodenum, we might have moderate
to severe lymphoplasmacytic enteritis.

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And so that makes it really hard for
the pathologist to know what's going on.

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Small cell lymphomas are almost always
diffuse, which means that they don't

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build masses or things like that.

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We see enlarged cell lymphomas
diffuse in the gut cell wall.

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So why is it difficult for
pathologists to differentiate?

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If we think about IBD in cats, most
experts would agree that lymphoplasmacytic

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enteritis is by far the most common
form of inflammatory bowel disease

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in dogs and cats, and that cellular
infiltrate consists of, again, small

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mature lymphocytes intermixed with plasma
cells and other inflammatory cells like

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neutrophils, eosinophils, or macrophages.

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In LGITL, the dominant cell infiltrate
are small mature lymphocytes.

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Which again can be intermixed
with other inflammatory cells.

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Think about these small lymphocytes,
a small mature cells also mean that

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there is a very low mitotic index, which
means, of course, that clinically this

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disease is progressing very slow and
so it almost has an indolent behaviour.

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All of us have encountered  cases
where we do see muscularis or

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mucosal layer thickening, or both.

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This disease, even though maybe
ultrasonographically we might see it in

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the muscularis, has no correlation with
anything, except for the mucosal changes.

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This really is a mucosal disease.

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Despite attempts from other studies,
nobody has found a cutoff that

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would definitively say, okay, if
the gut wall is this thick, or if

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the abdominal lymph nodes are this
thick, it would be definitely LGITL.

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It's really hard for the clinical
pathologist to make any diagnosis of

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small cell lymphoma just based on the
finding of small mature lymphocytes

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and some reactive lymphocytes.

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If we see that there's like sheets and
sheets of these monomorphic looking small

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lymphocytes that obliterate the entire
mucosa and don't make space for anything

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else, I think it's a pretty clear case.

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But then if we do have these nests
and plaques and accumulations

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of small lymphocytes, that's
when things get tricky.

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So other types of lymphoma that
we should not forget about is

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high grade large cell lymphomas.

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These can be either of
T or of B cell origin.

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High grade large cell could be both.

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They are often located in the ilium or the
iliopoietic junction or stomach and they

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often make masses, rather than diffused
lesions, but they can be diffused.

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And they can be in the
mucosal or transmural.

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When we do have severe, they often
produce severe abdominal lymphadenopathy,

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thickening of the bowel wall.

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They can also be in other organs and
cause hepatomegaly or splenomegaly.

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And those findings, of course,
we would find on abdominal

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ultrasound, which would be great.

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But I want to stress here, the absence
of ultrasonographic findings does

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not exclude large cell lymphomas.

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The absence of any findings in ultrasound
doesn't mean that there's nothing there.

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But the other thing that is fantastic
about ultrasound in that aspect is

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that we can do  fine needle aspirates.

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We might see sheets of large, very
immature lymphoblasts, that have cellular

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abnormalities, pleomorphism, multiple
nucleoli or even nuclei, present.

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And then if we are really lucky,
we might see actually mitosis.

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And so, this indicates that the
mitotic index is really high.

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Fine needle aspirates are really
phenomenal way of diagnosing the disease.

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And also if we think about that cellular
composition, it also becomes clear where

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that usually is a much more aggressive
clinical course because a higher mitotic

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index correlates with more rapid growth
and a more aggressive clinical course.

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That makes it clear why we shouldn't
treat that just with metronomic

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chemotherapy, but with more cytotoxic
chemotherapy, such as CHOP protocols.

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Some people call it a subform.

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Some call it a separate form.

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I want to talk about large
granular lymphocyte lymphomas.

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Similar to large cell lymphomas, these
are composed of large lymphocytes.

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They  make up about one third of
large cell lymphomas and consist

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of cytotoxic T cells or NK cells.

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Histologically,

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they're characterised by eosinophilic
granules in the cytoplasm.

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They can cause either mass like lesions,
but they can all or segmental thickening

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and they're often readily diagnosed
by fine needle aspirates as well.

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While large cell lymphomas have
a relatively poor prognosis,

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unfortunately, large granular lymphocyte
lymphomas have a grave prognosis

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and a very aggressive clinical

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course.

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Do you think the difference between
small cell lymphoma and inflammatory

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bowel disease is relevant?

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I think if it was me, I would want
my doctor to give me all the options

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and then I can decide, right?

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While I agree that a cat with
chronic intestinal disease likely

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has IBD or LGITL, there are
intermediate and large cell lymphomas.

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There's mast cell disease.

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There's infectious disease,
including histoplasmosis, at

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least here in the United States.

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There's gastrointestinal
eosinophilic sclerosing fibroplasia.

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All of those are important differentials
for cats with chronic GI disease, right?

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We mentioned that neither clinical
science, nor serological  testing,

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nor ultrasound, nor cytology, none
of those have been found to have, to

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reliably differentiate between the two.

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The only reliable way to differentiate
is to collect intestinal biopsies.

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The beauty of our profession, I believe,
is that there is no algorithm that

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works for every single patient, right?

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Because it depends so much on whether
I have a cat that has lost a lot

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of weight rapidly, according to
the owner, and maybe doesn't have

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so much time to do a diet trial.

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I might push harder for biopsies because
we just don't have much time to lose,

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versus in a cat that might be very stable,
I would suggest maybe a treatment trial.

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If I have a stable 10 year
old cat, otherwise healthy,

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maybe mildly underweight,

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the risk for taking
biopsies is really small.

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But if I have a cat with severe HCM,
obviously the calculation changes.

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I believe your question is the difference
between small cell lymphoma and  IBD

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relevant for therapeutic options, right?

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So it is true that many cats with
LGITL respond to prednisolone

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treatment alone, at least for a while.

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And then on the other hand, cats
which are refractory IBD can

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be treated with Chlorambucil.

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So in the real world, the treatment
is very similar currently.

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You might argue could you not
go on an escalating treatment

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regimen starting with Pred?

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Then assess and escalate
to Chlorambucil if need be?

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And I think again,
perfectly valid options.

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It's possible that we will see
better and more targeted therapies

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in the future, but currently the
treatment is very similar and you

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could argue there isn't a clinically
relevant difference at this point.

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Thank you so much.

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That's fascinating.

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Now over to Kelly St.

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Denis and Jonathan Stockman
to discuss dietary phosphorus

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and renal disease in cats.

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Welcome, Dr Stockman.

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Thank you

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Why is phosphorus important?

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Phosphorus is at the heart of
nutritional management of kidney

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disease in cats because a lot of
the derangements in hormones are to

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do with phosphorus metabolism with
chronic kidney disease in cats.

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When we have chronic kidney disease,
some of the things that may occur

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are we can have an increase in
the parathyroid hormone, which is

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obviously intimately involved in
regulating calcium and phosphorus.

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We may have a decrease ability
in the kidneys ability to  remove

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excess phosphorus from the body.

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We have less activation of vitamin
D, which is also important for

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calcium and phosphorus metabolism.

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So all of these things play together.

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When we have kidney disease and
contribute to the progression

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of disease and worsening of the
clinical status of the patient.

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We know we have to monitor phosphorus
because hyperphosphatemia is a

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negative indicator to address.

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High phosphorus and calcium also have
the risk of the calcium phosphorus

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product and mineralization of
tissues, which also contributes

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to the progression of the disease.

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So these are all things that come into
play together and can really impact the

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patient's wellbeing and how quickly they
progress through the disease, which is

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obviously what we're trying to prevent.

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We're trying to avoid the disease
from progressing as much as possible.

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In addition to  that, what I
highlighted in the paper as well is

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again the topic of excess dietary
phosphorus even in healthy adult cats.

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Our study was the first one to
show that these changes can happen

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very quickly if they receive a
lot of bioavailable phosphorus.

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And also that these changes are truly
indicative of kidney damage that leads

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to chronic kidney disease and not
something that is potentially reversible.

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In the article, you do talk about
monitoring dietary phosphorus,

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but other options such as
calcium to phosphorus ratio.

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And I wondered if you could tell us how
are we supposed to navigate this if it

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is so difficult for us to  monitor just
based on total dietary phosphorus alone?

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It's tricky because manufacturers
don't have to declare the total

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amount of phosphorus in the diet.

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Some provide information on the
label, but it's totally voluntary.

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Even when they do it's the total
dietary phosphorus, so we don't

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know how much is bioavailable.

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And you mentioned organic inorganic.

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And that's the type of language that
we've been using for a very long time.

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And in the literature there is some
evidence that suggests that the

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solubility of phosphorus in water
is crucial for the bioavailability.

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And it tends to be the inorganic
phosphors, salts that are water soluble,

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that are more bioavailable for cats.

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Those compounds are added to cat
food that can be very bioavailable

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and at high amounts, increasing the
risk for kidney damage and disease.

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There are other things that impact
phosphorus bioavailability, including

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the calcium to phosphorus ratio.

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When we have a higher ratio, it seems  to
reduce the bioavailability of phosphorus.

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So a calcium phosphorus ratio of
above one is safer in terms of

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high phosphorus risk of inducing
kidney disease than a low calcium to

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phosphorus ratio of let's say 0.5, 0.6.

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Also, the other thing that can
be a little bit protective is the

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amount of magnesium in the diet.

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So magnesium, together with
calcium, may complex with phosphorus

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preventing its absorption.

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So this is another thing
that can be helpful.

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But the calcium phosphorus ratio, you
can find the relative bioavailability

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of, and so obviously, when the calcium
and phosphorus ratio is a little

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bit higher, it's a little bit more
protective or the bioavailability is a

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little bit reduced for the phosphorus.

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And this is something that potentially
you can find on the label if the

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manufacturer decides that they want to
list it, but again, this is voluntary.

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And usually, that will be a minimum
value  analysed in the diet, but it

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doesn't tell you what the maximum is.

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So it's a bit of a limited information.

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Where do early kidney and kidney
disease diets fall into this, in

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terms of making decisions about that?

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If you're a newly diagnosed cat in very
early stages of kidney disease to start

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with those early disease diet, especially
when they're  in stages one through two.

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But then one of the monitoring steps
that I would consider is maybe at that

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point, when they're on the diet for a
little while, still measuring PTH and

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FDF23 and then if elevated, transition
to a more phosphorus restricted diet.

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If those hormones are very elevated, that
can be an indication that we could benefit

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from even more phosphorus reduction.

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There is evidence that FGF23
elevation on its own is a negative

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and can lead to cardiovascular
disease and other complications.

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So it is something we should consider.

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Thank you.

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Thank you all for listening.

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If you are an ISFM member don’t forget
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If you are looking for more free
CPD from ISFM in November we have

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a number of open access webinars.

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First up, on the 19th we have a
webinar on Microbiota analysis,

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evidence and perspectives on
clinical practice for vets.

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And thats with Miquel
Montserrat and that’s brought

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to you by Purina.

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On the 25th of November, we have our
final Cat Friendly Clinic webinar

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for the year, that’s on Cat Friendly
Hospitalisations, with Yaiza Gomez Meijas.

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We'll be back again next month,
with more from the world of

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feline medicine and JFMS.